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Studies on pharmacokinetics of tetrodotoxin in the puffer fish and tetrodotoxin-transporter in the liver

Research Project

Project/Area Number 20380120
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Fisheries chemistry
Research InstitutionTokyo University of Marine Science and Technology

Principal Investigator

NAGASHIMA Yuji  Tokyo University of Marine Science and Technology, 海洋科学部, 教授 (40180484)

Co-Investigator(Renkei-kenkyūsha) ISHIZAKI Shoichiro  東京海洋大学, 海洋科学部, 准教授 (40251681)
Research Collaborator MATSUMOTO Takuya  東京海洋大学, 海洋科学部, 博士研究員
TERAO Isaki  東京海洋大学, 大学院・海洋科学技術研究科, 博士前期課程
TSUTSUMI Kazuma  東京海洋大学, 海洋科学部, 学部生
Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥15,730,000 (Direct Cost: ¥12,100,000、Indirect Cost: ¥3,630,000)
Fiscal Year 2010: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2009: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2008: ¥8,060,000 (Direct Cost: ¥6,200,000、Indirect Cost: ¥1,860,000)
Keywordsフグ / テトロドトキシン / 体内動態 / 薬物動態解析 / 消化管吸収 / 血漿タンパク質結合 / トランスポーター / cDNAサブトラクション / フグ毒 / ペプシジン / 生体防御 / 反転腸管法 / 血液運搬
Research Abstract

Puffer fish, the family Tetraodontidae, contain a potent neurotoxin, tetrodotoxin (TTX) in high level in the specific tissues such as liver and ovary. However, the underlying mechanism of puffer fish toxification is still unclear. This study examined the pharmacokinetics of TTX in the puffer fish Takifugu rubripes by a single administration and demonstrated that TTX is absorbed into the systemic circulation from the gastrointestinal tract by saturable mechanism and finally accumulated in the liver. In vitro equilibrium dialysis revealed that TTX non-specifically binds to plasma proteins and exists predominately in the unbound form in the circulating blood of the puffer fish. Moreover, we examined hepatic gene expression profile of the puffer fish by suppression subtracted hybridization in response to the intramuscular administration of TTX. The administration of TTX increased the gene expression of the acute-phase response proteins in the liver as well as the genes related to transporters.

Report

(4 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (38 results)

All 2011 2010 2009 2008 Other

All Journal Article (11 results) (of which Peer Reviewed: 7 results) Presentation (14 results) Book (2 results) Remarks (11 results)

  • [Journal Article] Differential gene expression profile in the liver of the marine puffer fish Takifugu rubripes induced by intramuscular administration of tetrodotoxin2011

    • Author(s)
      T.Matsumoto, S.Ishizaki, Y.Nagashima
    • Journal Title

      Toxicon 57巻

      Pages: 304-310

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Differential gene expression profile in the liver of the marine puffer fish Takifugu rubripes induced by intramuscular administration of tetrodotoxin2011

    • Author(s)
      T.Matsumoto G
    • Journal Title

      Toxicon

      Volume: 57 Pages: 304-310

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Plasma protein binding of tetrodotoxin in the marine puffer fish Takifugu rubripes2010

    • Author(s)
      T.Matsumoto, D.Tanuma, K.Tsutsumi, J.-K.Jeon, S.Ishizaki, Y.Nagashima
    • Journal Title

      Toxicon 55巻

      Pages: 415-420

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Plasma protein binding of tetrodotoxin in the marine puffer fish Takifugu rubripes2010

    • Author(s)
      T.Matsumoto, 等
    • Journal Title

      Toxicon 55

      Pages: 415-420

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 魚類の毒(1)フグ毒2009

    • Author(s)
      長島裕二, 松本拓也
    • Journal Title

      食品衛生研究 59巻7号

      Pages: 43-51

    • Related Report
      2010 Final Research Report
  • [Journal Article] 魚類の毒 (1) : フグ毒2009

    • Author(s)
      長島裕二, 等
    • Journal Title

      食品衛生研究 59巻7号

      Pages: 43-51

    • Related Report
      2009 Annual Research Report
  • [Journal Article] Evaluation of hepatic uptake clearance of tetrodotoxin in the puffer fish Takifugu rubripes2008

    • Author(s)
      T.Matsumoto, Y.Nagashima, H.Kusuhara, S.Ishizaki, K.Shimakura, K.Shiomi
    • Journal Title

      Toxicon 52巻

      Pages: 369-374

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Pharmacokinetics of tetrodotoxin in puffer fish Takifugu rubripes by a single administration technique2008

    • Author(s)
      T.Matsumoto, Y.Nagashima, H.Kusuhara, S.Ishizaki, K.Shimakura, K.Shiomi
    • Journal Title

      Toxicon 51巻

      Pages: 1051-1059

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] フグにおけるフグ毒体内動態2008

    • Author(s)
      松本拓也, 長島裕二
    • Journal Title

      食品衛生学雑誌 49巻6号

    • Related Report
      2010 Final Research Report
  • [Journal Article] フグにおけるフグ毒体内動態2008

    • Author(s)
      松本拓也
    • Journal Title

      食品衛生学雑誌 49

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Pharmacokinetics of tetrodotoxin in marine puffer fish Takifugu rubripes2008

    • Author(s)
      T. Matsumoto
    • Journal Title

      Proceedings of 5th World Fisheries Congress 2008 (CD版)

    • Related Report
      2008 Annual Research Report
  • [Presentation] Hepatic uptake mechanism of tetrodotoxin in the pufferfish Takifugu rubripes2010

    • Author(s)
      長島裕二
    • Organizer
      International conference on risk assessment of marine toxins in seafood
    • Place of Presentation
      国立台湾海洋大学(中華民国基隆市)
    • Year and Date
      2010-11-05
    • Related Report
      2010 Final Research Report
  • [Presentation] Hepatic uptake mechanism of tetrodotoxin in the pufferfish Takifugu rubripes2010

    • Author(s)
      Y.Nagashima
    • Organizer
      International conference on risk assessment of marine toxins in seafood
    • Place of Presentation
      中華民国基隆市(国立台湾海洋大学)
    • Year and Date
      2010-11-05
    • Related Report
      2010 Annual Research Report
  • [Presentation] フグ毒投与はトラフグ肝臓でのHepcidin発現を誘導する2010

    • Author(s)
      松本拓也, 石崎松一郎, 長島裕二
    • Organizer
      平成22年度日本水産学会春季大会
    • Place of Presentation
      日本大学生物資源科学部(神奈川県藤沢市)
    • Year and Date
      2010-03-28
    • Related Report
      2010 Final Research Report
  • [Presentation] 反転腸管法によるテトロドトキシンの消化管吸収測定2010

    • Author(s)
      寺尾依咲, 松本拓也, 石崎松一郎, 長島裕二
    • Organizer
      平成22年度日本水産学会春季大会
    • Place of Presentation
      日本大学生物資源科学部(神奈川県藤沢市)
    • Year and Date
      2010-03-27
    • Related Report
      2010 Final Research Report
  • [Presentation] Pharmacokinetics and hepatic uptake of tetrodotoxin in the marine puffer fish Takifugu rubripes2009

    • Author(s)
      松本拓也, 石崎松一郎,, 長島裕二
    • Organizer
      International symposium on seafood processing technology and safety control system
    • Place of Presentation
      中国海洋大学(中国青島市)
    • Year and Date
      2009-11-01
    • Related Report
      2010 Final Research Report
  • [Presentation] Pharmacokinetics and hepatic uptake of tetrodotoxin in the marine puffer fish Takifugu rubripes2009

    • Author(s)
      T.Matsumoto, ら
    • Organizer
      International symposium on seafood processing technology and safety control system
    • Place of Presentation
      中国青島市
    • Year and Date
      2009-11-01
    • Related Report
      2009 Annual Research Report
  • [Presentation] トラフグ血漿タンパク質とテトロドトキシンの結合親和性2009

    • Author(s)
      松本拓也, 田沼大輔, 堤一磨, 石崎松一郎, 長島裕二
    • Organizer
      平成21年度日本水産学会秋季大会
    • Place of Presentation
      いわて県民情報交流センター(岩手県盛岡市)
    • Year and Date
      2009-10-01
    • Related Report
      2010 Final Research Report
  • [Presentation] トラフグ血漿タンパク質とテトロドトキシンの結合親和性2009

    • Author(s)
      松本拓也, ら
    • Organizer
      平成21年度日本水産学会秋季大会
    • Place of Presentation
      岩手県盛岡市
    • Year and Date
      2009-10-01
    • Related Report
      2009 Annual Research Report
  • [Presentation] トラフグ毒化過程における遺伝子発現解析2009

    • Author(s)
      松本拓也, 石崎松一郎, 長島裕二
    • Organizer
      平成21年度日本水産学会春季大会
    • Place of Presentation
      東京海洋大学(東京都港区)
    • Year and Date
      2009-03-30
    • Related Report
      2010 Final Research Report
  • [Presentation] トラフグ毒化過程における遺伝子発現解析2009

    • Author(s)
      松本拓也ら
    • Organizer
      平成21年度日本水産学会春季大会
    • Place of Presentation
      東京都港区
    • Year and Date
      2009-03-29
    • Related Report
      2008 Annual Research Report
  • [Presentation] トラフグ体内におけるフグ毒テトロドトキシンの薬物動態解析2008

    • Author(s)
      松本拓也, 石崎松一郎, 長島裕二, 嶋倉邦嘉, 塩見一雄
    • Organizer
      トランスポーター研究会第2回関東部会
    • Place of Presentation
      東京大学(東京都文京区)
    • Year and Date
      2008-12-06
    • Related Report
      2010 Final Research Report
  • [Presentation] トラフグ体内におけるフグ毒テトロドトキシンの薬物動態解析2008

    • Author(s)
      松本拓也ら
    • Organizer
      トランスポーター研究会
    • Place of Presentation
      東京都文京区
    • Year and Date
      2008-12-06
    • Related Report
      2008 Annual Research Report
  • [Presentation] Pharmacokinetics of tetrodotoxin in marine puffer fish Takifugu rubripes2008

    • Author(s)
      松本拓也, 石崎松一郎,, 長島裕二, 嶋倉邦嘉, 塩見一雄
    • Organizer
      5th World Fisheries Congress 2008
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2008-10-23
    • Related Report
      2010 Final Research Report
  • [Presentation] Pharmacokinetics of tetrodotoxin in marine puffer fish Takifugu rubripes2008

    • Author(s)
      T. Matsumotoら
    • Organizer
      5th World Fisheries Congress 2008
    • Place of Presentation
      神奈川県横浜
    • Year and Date
      2008-10-23
    • Related Report
      2008 Annual Research Report
  • [Book] Pharmacokinetic studies on uptake mechanism of tetrodotoxin in the puffer fish Takifugu rubripes. Comprehensive Bioactive Natural Products Volume 3. Efficacy, Safety & Clinical Evaluation II2010

    • Author(s)
      T.Matsumoto, Y.Nagashima
    • Publisher
      Studium Press LLC
    • Related Report
      2010 Final Research Report
  • [Book] Comprehensive Bioactive Natural Products Volume 3 Efficacy, Safety & Clinical Evaluation II2010

    • Author(s)
      T.Matsumoto, Y.Nagashima
    • Publisher
      Studium Press LLC, U.S.A.
    • Related Report
      2010 Annual Research Report
  • [Remarks] 研究室

    • URL

      http://www2.kaiyodai.ac.jp/~ishizak/

    • Related Report
      2010 Final Research Report
  • [Remarks] 東京海洋大学研究者総覧データベース

    • URL

      http://olcr.kaiyodai.ac.jp/

    • Related Report
      2010 Final Research Report
  • [Remarks] 長島裕二:ふぐの安全性東京都ふぐ卸売協同組合セミナー2009年8月25日東京都中央区

    • Related Report
      2010 Final Research Report
  • [Remarks] 長島裕二:ふぐの安全性に関する知識全国ふぐ連盟第29回定時総会ふぐシンポジウム2009年7月8日神奈川県横浜市

    • Related Report
      2010 Final Research Report
  • [Remarks] 長島裕二:フグの安全性平成20年度神奈川県ふぐ包丁師衛生講習会2009年3月19日神奈川県横浜市

    • Related Report
      2010 Final Research Report
  • [Remarks] 長島裕二:ふぐはどうして毒をもつ薬物動態解析によるアプローチ長崎大学特別講義2008年12月17日長崎県長崎市

    • Related Report
      2010 Final Research Report
  • [Remarks] 長島裕二:フグの衛生知識平成20年度遊漁船フグ取扱者技術講習会2008年8月4,5,29日茨城県ひたちなか市

    • Related Report
      2010 Final Research Report
  • [Remarks] 茨城新聞2008年8月4日全国初食中毒防止へ新資格遊漁船にフグ取扱者

    • Related Report
      2010 Final Research Report
  • [Remarks] 読売新聞茨城地方版2008年8月6日釣り船業者にフグ処理資格規制広げて中毒死防げ

    • Related Report
      2010 Final Research Report
  • [Remarks]

    • URL

      http://www2.kaiyodai.ac.jp/~ishizak/

    • Related Report
      2010 Annual Research Report
  • [Remarks]

    • URL

      http://www2.kaiyodai.ac.jp/~ishizak/

    • Related Report
      2008 Annual Research Report

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Published: 2008-04-01   Modified: 2016-04-21  

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